Xy. Gui et al., Endogenous neurotensin facilitates enterohepatic bile acid circulation by enhancing intestinal uptake in rats, AM J P-GAST, 281(6), 2001, pp. G1413-G1422
Citations number
56
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Initial studies on the digestive hormone neurotensin (NT) showing that inte
stinal NT mRNA expression and blood levels were altered in rats fed chow co
ntaining bile acid (BA) and the BA chelator cholestyramine led us to invest
igate the role of NT in the enterohepatic circulation of BA. In fasted, ane
sthetized rats with common bile ducts cannulated for bile collection, intra
venous NT infusion (10 pmol.kg(-1).min(-1)) enhanced BA output relative to
control over 3 h in animals administered donor bile into the duodenum (30 m
ul/min). This suggested that the effect of NT was on the return of BA from
the intestine to the liver, which is rate determining in the normal process
. In rats prepared as described above and administered [H-3]taurocholate ([
H-3]TC; 5 mM, 1 ml) duodenally, NT infusion (3-10 pmol.kg(-1).min(-1)) incr
eased the [H-3]TC recovery rate in bile approximately twofold, whereas sulf
ated CCK-8 (12-50 pmol.kg(-1).min(-1)) had no effect. To investigate the ro
les of endogenous NT and CCK, we administered [H-3]TC into the rat duodenum
or lower jejunum and tested the effect of the NT antagonist SR-48692 (2 nm
ol.kg(-1).min(-1)) or CCK-A antagonist lorglumide (100 nmol.kg(-1).min(-1))
. SR-48692 reduced the [H-3]TC recovery rate by congruent to 50% and congru
ent to 24% in the duodenum and jejunum, respectively, whereas lorglumide ha
d no effect. These results suggest that NT or a similar peptide is an endog
enous regulator of enterohepatic BA cycling, which acts by enhancing BA upt
ake in the intestine.